Cardenal was ordained a Catholic priest in 1965 in Granada.[1] He went to the Solentiname Islands where he founded a Christian, almost monastic, mainly peasant community, which eventually led to the founding of the artists' colony. It was there that the famous book El Evangelio de Solentiname ("The Gospel of Solentiname") was written. Cardenal collaborated closely with the leftistFrente Sandinista de Liberación Nacional (Sandinista National Liberation Front, or FSLN), in working to overthrow Anastasio Somoza Debayle's régime.

Many members of the community of Solentiname engaged with the process of the Revolution, in the guerrilla warfare that the FSLN had developed to strike at the regime. 1977 was a crucial year to Cardenal's community since Somoza's National Guard, as a result from an attack to the headquarters stationed in the city of San Carlos, a few miles from the community, raided Solentiname and burned it to the ground, with Cardenal fleeing to Costa Rica.

On 19 July 1979, immediately after the Liberation of Managua, he was named Minister of Culture by the new Sandinista regime. He campaigned for a "revolution without vengeance"[2] His brother Fernando Cardenal, also a Catholic priest (in the Jesuit order), was appointed Minister of Education. When Pope John Paul II visited Nicaragua in 1983, he openly scolded Ernesto Cardenal, who knelt before him, on the Managua airport runway, for resisting his order to resign from the government. The Pope admonished Cardenal: Usted tiene que arreglar sus asuntos con la Iglesia ("You must fix your affairs with the Church"). Cardenal remained minister of Culture until 1987, when his ministry was closed due to economic reasons.

Cardenal left the FSLN in 1994, protesting the authoritarian direction of the party under Daniel Ortega but insists that he has retained his leftist opinions. He is a member of the Movimiento de Renovación Sandinista (Sandinist Renovation Movement, MRS) that participated in the 2006 Nicaraguan General Elections. Days before the election, Cardenal stated, in a clear reference to his dispute with Ortega, that "I think it would be more desirable an authentic capitalism, as Montealegre's (Eduardo Montealegre, the presidential candidate for Alianza Liberal Nicaragüense) would be, than a false Revolution".[3]

Cardenal has been for a long time a polemical figure of Nicaragua's literature and cultural history. He has been described as "the most important poet right now in Latin America",[4] politically and poetically, he has been a very vocal figure of Nicaragua, and a valid key to analyze and understand the contemporaneous literary and cultural life of Nicaragua. He participated in the Stock Exchange of Visions project in 2007.

During a short visit to India he came in touch with a group of writers called the Hungry generation, which had a profound influence on them.